1. Field of the Invention
This invention relates to a target substance detecting element, a target substance detection apparatus and a target substance detection method adapted to cause a target substance, e.g. proteins and DNAs, in a specimen to react highly efficiently with captors fixed to a piece of metal to improve the sensitivity of detection of the target substance.
2. Related Background Art
A number of markers (marker genes) of specific diseases such as cancer, hepatitis, diabetes mellitus, osteoporosis and so on exist in blood. The concentration of a specific protein increases in a subject when the subject contracts any of such diseases from the level observed in the healthy body of the subject. Therefore, it is possible to detect any of such serious diseases in earlier stages of contraction by monitoring the related proteins. Thus, techniques for monitoring proteins are expected to be used effectively in the next generation. One of the known techniques for analyzing unprocessed and unrefined proteins is based on a sensor for identifying a specific chemical compound by utilizing the biological ligand-analyte interaction.
Several types of sensors are known to date. Known sensors include those that utilize fluorescent immunoassay, those that utilize magnetic immunoassay and those that utilize plasmon resonance. However, all of them have a common step of fixing a ligand to the surface of the sensor and causing it to be selectively bonded to the analyte in an object of detection in a highly selective and sensitive manner in order to eliminate impurities and highly efficiently fix the desired proteins to the surface of a substrate. In the case of fluorescent immunoassay, a second ligand that is marked by a fluorescent dye is bonded to a ligand-analyte complex and the fluorescent dye is energized to observe the quantity of fluorescence and hence the concentration of analyte. In the case of magnetic immunoassay, a second ligand that is marked by a magnetic bead is bonded to a ligand-analyte complex to observe the change in the magnetic field and hence the concentration of analyte. In the case of plasmon resonance, the concentration of analyte is observed on a ligand-analyte complex formed on a metal thin film or a metal fine particle by utilizing the fact that a metal plasmon highly sensitively reacts to the change in the refractive index of the surface substance.
Japanese Patent No. 3452837 discloses a plasmon resonance sensor adapted to fix Au fine particles to the surface of a glass substrate and detect the change in the refractive index of a solvent or the extent of antigen adsorption in an antigen-antibody reaction. A sensor according to the cited invention can be arranged in a narrow place and advantageously be used for a specimen of any form.
Japanese Patent Application Laid-Open No. 2004-93558 discloses an apparatus for highly efficiently detecting the process where an object of measurement and a specific substance are bonded to and dissociated from each other by combining diffraction grating type SPR (surface plasmon resonance) with a micro channel chip to minimize the quantity of introduction of a specimen and washing liquid.
There is a document disclosing a method of preparing core-shell type fine particles by coating ferrite with gold and observing optical characteristics (absorption spectrum) thereof (NANO LETTERS, 2004, vol. 4, No. 4, p 719-723).
With the technique disclosed in Japanese Patent Application Laid-Open No. 2004-93558, diffusion-controlling due to the appearance of concentration gradient of the target substance is suppressed by injecting a specimen into a very small flow path and transferring it by liquid in order to cause the target substance to highly efficiently react with captors. Then, the concentration of the target substance captured by the fixed captors is detected by detecting the change in the plasmon resonance. In other words, the cited invention requires a special structure for suppressing diffusion-controlling due to the appearance of concentration gradient of the target substance when the specimen is brought to contact with the surface where plasmon resonance is generated. In other words, the conventional art needs improvements.